The purpose of the proposed research is the study of the physiology of central neuroendocrine regulation. Our major objective is to define the neural circuitry involved in this regulation both anatomically and functionally. To this end, we propose to study the hypothalamic releasing factors, TRH, LHRH, somatostatin and MIF to determine where in brain they are made, whether they function as neurotransmitters, whether releasing factor receptors in brain have a functonal significance and whether prohormones or functional analogues of those compounds exist. We also propose to continue our neurotransmitter mapping studies to determine what pathways and what particular types of neurons within these pathways innervate areas which contain releasing factors. Furthermore we propose to study the physiology of each of these innervative pathways to discover what type of neuron influences the secretion of releasing factors from the medial basal hypothalamus and in what area of brain and under what circumstances this influence occurs. Finally we propose to study the physiology of the circumventricular organs, small vascular subependymal structures in brain whose function is as yet unknown, but which may function as a CNS-systemic circulation communication site and which contain large amounts of releasing factors and neurogenic amines. Our method will be based on neurosurgical skills utilizing a stereotaxic apparatus, the microdissection techniques of Palkovits, sensitive microchemical methods for dopamine, norepinephrine, serotonin, glutamic acid decarboxylase, tyrosine hydroxylase, dopamine-beta-hydroxylase, tryptophane hydoxylase, choline acetyltransferase and substance P; and radioimmunoassays for TRH, LHRH and somatostatin, methods with which we have had experience and which are all available in our laboratory. The advantages of such an approach to the elucidation of the neural circuitry of endocrine regulation result from our ability to study various structures in brain specifically, quantitatively and in minute anatomical detail. Finally, it is hoped that the research of this project will enable the formulation of a basic neurophysiology of endocrine function. Development of information of this kind will permit a greater understanding of the role of the brain and its functional set (Text Truncated - Exceeds Capacity)